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Identifying the main predictors of urine output in autosomal-dominant polycystic kidney disease (ADPKD) patients taking tolvaptan

  • Nephrology - Original Paper
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Abstract

Background

Few works have analyzed factors associated with urine output in ADPKD patients taking tolvaptan (TVP).

Methods

We selected 24-h urine samples from ADPKD patients treated with TVP. Urine osmolality/creatinine ratio was used as estimator of urinary osmolar load.

Results

We included 127 urine samples from 61 patients. After TVP, urine output doubled with a parallel reduction in urine solute concentration. However, when expressed as urine solute/creatinine ratios, no significant changes were observed. Daily osmolar load and osmolality/creatinine ratio did not change significantly.

Before TVP, urine output was positively correlated with body weight and urine osmolality/creatinine ratio and negatively with eGFR, urine morning osmolality, and 24-h urine-calculated osmolality. After TVP, urine output was positively correlated with body weight, eGFR and negatively with age. There was a poor correlation with urine-calculated osmolality.

We constructed a predictor model using mixed-effects modeling and we found that urine output was related to lower age, higher body weight, higher eGFR, and greater doses of TVP. When body weight was removed, urine output was also related to male sex and a higher daily osmolar excretion. Equation of prediction was: Urine output (mL/day) = 2771–52.9 × Age (years) + 58.4 × Weight (kg) + 18.7 × eGFR (mL/min) + 870 (if TVP = 90/30 mg) + 517 (if TVP = 60/30 mg).

Conclusion

Patients taking TVP will undergo an increase about twice in urine production from baseline. Greater doses of TVP cause a progressive increase in urine production. GFR, age, and body weight are the main predictors of future urine output in patients taking TVP.

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Data availability

Date are not available for authors not participating in this study.

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Funding

This study was not supported by any funding.

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Authors and Affiliations

  1. Unidad de Gestión Clínica (UGC) de Nefrología, Hospital Universitario de Jaén, Jaén, Spain

    Francisco José Borrego Utiel & Enoc Merino García

  2. Servicio de Nefrología, Hospital Universitario Clínico San Cecilio, Granada, Spain

    Ana Isabel Morales García

  3. UGC de Nefrología, Hospital Universitario Virgen de Las Nieves, Granada, Spain

    Aurora Polo Moyano & Rafael Esteban de la Rosa

  4. UGC de Nefrología, Hospital Universitario Virgen del Rocío, Seville, Spain

    Francisco Roca Oporto

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  1. Francisco José Borrego Utiel
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  2. Ana Isabel Morales García
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Contributions

FJBU conceived the study. FJBU, AIMG, APM, FRO, EMG, and RER collected the data. FJBU analyzed the data. FJBU and RER wrote the manuscript. All authors provided critical feedback and helped shape the research. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Francisco José Borrego Utiel.

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Conflict of interest

The results presented in this article have not been published previously in whole or part, except in abstract format. F.J.B.U. has received lecture fees and travel support from Otsuka. R.E.R. has received grant funding for meeting organizations and travel support from Otsuka.

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Supplementary Information

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11255_2023_3555_MOESM1_ESM.pptx

Supplementary file1 Twenty-four hour-urine output in ADPKD patients treated with tolvaptan. Urine output increased significantly from baseline with each dose of tolvaptan, but with a high dispersion in individual response. (PPTX 61 KB)

11255_2023_3555_MOESM2_ESM.pptx

Supplementary file2 Twenty-four hour-urine output increased progressively after treatment with tolvaptan in ADPKD patients in all doses in both sexes. There were no differences in urine production between sex when considering each dose separately. (PPTX 61 KB)

11255_2023_3555_MOESM3_ESM.pptx

Supplementary file3 A. Urine output was midly correlated with daily osmolar load expressed as OsmU/CrU in 24 h-urine at baseline in ADPKD patients. B. After tolvaptan, urine output did not correlated with OsmU/CrU ratio. (PPTX 110 KB)

11255_2023_3555_MOESM4_ESM.pptx

Supplementary file4 A. Before treatment with tolvaptan, ADPKD patients showed a negatively correlation between 24 h-urine output and calculated urinary osmolality in 24 h-urine. B. After starting treatment with tolvaptan, we observed a poor correlation between both variables. (PPTX 106 KB)

11255_2023_3555_MOESM5_ESM.pptx

Supplementary file5 A. At baseline, 24-urine output was negatively correlated with morning urinary osmolality in ADPKD patients. B. After tolvaptan treatment, there was no correlation between both variables. (PPTX 98 KB)

11255_2023_3555_MOESM6_ESM.pptx

Supplementary file6 Predicted values of 24 h-urine output using equation built with linear mixed-effects modelling (see Table 2) for several values of sex, age, glomerular filtration rate, weight and doses of tolvaptan. (PPTX 53 KB)

Supplementary file7 (DOCX 14 KB)

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Utiel, F.J.B., García, A.I.M., Moyano, A.P. et al. Identifying the main predictors of urine output in autosomal-dominant polycystic kidney disease (ADPKD) patients taking tolvaptan. Int Urol Nephrol 55, 2629–2637 (2023). https://doi.org/10.1007/s11255-023-03555-8

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